The present invention relates to novel morpholino compounds, processes for the preparation thereof, the use of the compounds in compositions for the treatment of the oral cavity, especially the tooth surfaces, and for the inhibition or removal of dental plaque, and a method of keeping the tooth surface clean.
The novel morpholino derivatives according to this invention are represented by the following general formula: ##STR2## wherein R.sub.1 is a straight or branched alkyl group containing 8 to 16 carbon atoms at the 2- or 3-position of the morpholino ring, and R.sub.2 is a straight or branched alkyl group containing 2 to 10 carbon atoms, substituted with a hydroxy group except in the alpha-position. The sum of the carbon atoms in the groups R.sub.1 and R.sub.2 is at least 10 and preferably 10 to 20.
The novel compounds of the formula I above have valuable properties for maintaining the oral cavity hygiene since when applied to the tooth surfaces in solution or in a composition they inhibit the formation of dental plaque and also have the ability to remove plaque already formed. For this reason they prevent especially dental caries, gingivitis and parondontitis. The compounds do not exhibit a pronounced antibacterial effect, which is of importance for the maintenance of a normal bacterial status in the oral cavity and in the intestinal tract.
The novel compounds according to the invention can be prepared according to several processes, especially the following:
(a) by alkylating a morpholino derivative having the formula ##STR3## wherein R.sub.1 is as defined above; with an alkylating agent of the formula EQU R.sub.2 X III
wherein R.sub.2 is as defined above and X is halogen or an organic sulfonic ester, or wherein X together with a hydroxyl group present in R.sub.2 is a reactive oxide;
(b) by ring closure of a compound having the general formula ##STR4## wherein R.sub.1 is as defined above, X is halogen or an organic sulfonic ester and A represents CH.sub.2 groups, one CH.sub.2 group being substituted with the group R.sub.1 ; with an amino alkanol of the general formula EQU NH.sub.2 R.sub.2 V
wherein R.sub.2 is as defined above;
(c) by reducing a mono- or di-oxo substituted morpholine having the general formula ##STR5## wherein R.sub.2 is as defined above, n is 0 or 1, and R.sub.1 is as defined above and is at the 2-position when n is 1 and at the 2- or 3-position when n is 0, for the preparation of a compound of formula I;
(d) by starting from a morpholino compound having the general formula ##STR6## wherein R.sub.1 is as defined above and R.sub.3 is a straight or branched alkyl group containing a group transformable to OH or CH.sub.2 OH; especially
(d1) by converting a compound of the formula VIII, wherein the group in R.sub.3 transformable to OH is halogen, NHAc, OAc, O-alkyl, O--CH.sub.2.C.sub.6 H.sub.5 ; or
(d2) by converting a compound of the formula VIII, wherein the group in R.sub.3 transformable to CH.sub.2 OH is --COOC.sub.2 H.sub.5, --CN, --CHO; or
(d3) R.sub.3 represents --CO(CH.sub.2).sub.n --COOC.sub.2 H.sub.5 (n=0-8).